ADAMTS1 Is Required for Ventral Abdominal Wall Closure.

ADAMTS1 (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 repeats) is a secreted metalloproteinase with a known role in extracellular matrix remodeling in cardiovascular development and female fertility. Because of conflicting report of embryonic lethality and survival in Adamts1 mutant mice, we report generation and characterization of a new knockout (KO) allele, which led to detection of neonatal lethal omphalocele (persistent umbilical hernia) as a new Adamts1-dependent birth defect. This phenotype was also detected in another mutants with an in-frame lacZ insertion. β-galactosidase staining in the latter showed that Adamts1 was strongly expressed in the undifferentiated cells in the developing ventral abdominal wall preceding midline fusion at the umbilical cord attachment site. The omphalocele was characterized by the accumulation of the proteoglycan versican along with reduced proteolysis and impaired development of the superficial muscle layer, the panniculus carnosus, around the site of umbilical cord attachment. Furthermore, we observed sustained expression of the transcription factor, paired-like homeodomain transcription factor 2 in KO embryos, whereas it was downregulated in wild-type embryos during late embryogenesis. ADAMTS1 is thus a new matrisome component required for body wall closure.